1. The Invention
This invention relates to prostaglandin derivatives and intermediates for such derivatives and to methods of preparing such intermediates and derivatives. In a further aspect this invention relates to 10-substituted prostaglandin derivatives thereof and to methods of preparing such derivatives. In a still further aspect the invention relates to 10-substituted prostaglandins of the PGE.sub.1, PGE.sub.2, PGF.sub.1.sub..alpha. and PGF.sub.2.sub..alpha. series, the corresponding 5,6-substituted derivatives of such PGE.sub.1 and PGF.sub.1.sub..alpha. series, and esters and ethers thereof and methods of preparing such 10-substituted prostaglandins.
In another aspect this invention relates to amide derivatives and pharmaceutically acceptable salts of such 10-substituted prostaglandins.
2. The Prior Art
Prostaglandins are a group of chemically related 20-carbon chain hydroxy fatty acids having the basic skeleton of prostanoic acid: ##SPC1##
The prostaglandins having a keto group at the C-9 position are known as the PGE series, those having a hydroxyl group in place of the keto group are known as the PGF series and are further designated by an .alpha. or .beta. suffix to indicate the configuration of the hydroxyl group at said position. The natural compounds are the .alpha.-hydroxy substituted compounds. They may contain different degrees of unsaturation in the molecule, particularly at C-5, C-13 and C-17, the unsaturation is also indicated by a suffix. For a review on prostaglandins and the definition of primary prostaglandins, see for example S. Bergstrom, Recent Progress in Hormone Research 22 pp. 153-175 (1966) and Science 157, 382 (1967) by the same author.
Prostaglandins are widely distributed in mammalian tissues and have been isolated from natural sources in very small amounts. In addition a number of the natural occurring prostaglandins have been prepared by chemical synthesis; note, for example, J. Am. Chem. Soc. 91, 5675 (1969), J. Am. Chem. Soc. 92, 2586 (1970) and J. Am. Chem. Soc. 93, 1489-1493 (1971) and reference cited therein, W. P. Schneider et al, J. Am. Chem. Soc. 90, 5895 (1968), U. Axen et al, Chem. Commun, 303 (1969), and W. P. Schneider, Chem. Commun. 304 (1969).
Because of the remarkable range of biological and pharmacological properties exhibited by this family of compounds, a great deal of interest has focused upon such compounds and accordingly we have discovered a new group of prostaglandin derivatives which exhibit general prostaglandin pharmacological and biological properties.